Novel assay based on diluted prothrombin time reflects anticoagulant effects of direct oral factor Xa inhibitors: Results of multicenter study in Japan.

BACKGROUND: Direct oral anticoagulants targeting factor Xa (DXaIs) are administered as prophylaxis for various venothrombotic diseases without routine monitoring required. However, assessment of their anticoagulant effects is necessary to prevent severe events, including major bleeding and/or refractory thrombosis. OBJECTIVES: We examined the correlation of ratio of inhibited thrombin generation (RITG), determined using a novel assay based on dilute prothrombin time (dPT), with coagulant markers and laboratory test results to show drug effects. In addition, RITG usefulness as a confirmation test for DXaI therapy was investigated. METHODS: Citrated plasma samples were obtained from patients treated with rivaroxaban (n = 882), apixaban (n = 1214), or edoxaban (n = 820) at 4 different institutions in Japan. Laboratory tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and plasma concentrations of DXaIs, were conducted, with drug concentrations divided into peak and trough groups, within and after 5 h of administration. RESULTS: In each DXaI group, RITG was positively correlated with PT, APTT, and drug concentration, and negatively with D-dimer. RITG fluctuation during the peak and trough periods reflected the anticoagulant activity characteristic of each DXaI, which was different from blood concentration fluctuations. RITG showed a significant decrease in cases with thrombosis, while that was increased in those with hemorrhage. CONCLUSION: We developed RITG, a novel measurement method based on dPT. RITG represents residual coagulation ability in plasma samples, and is useful for assessment of bleeding and thrombotic tendencies in DXaI patients. RITG can be utilized to confirm the effectiveness of oral anticoagulation therapy with DXaI agents.

Regional Clinical Alliance Path and Cardiac Rehabilitation After Hospital Discharge for Acute Myocardial Infarction Patients in Japan　- A Nationwide Survey.

BACKGROUND: The regional clinical alliance path (RCAP) after discharge from an acute-phase hospital is emerging as a tool for bridging acute-phase treatment and chronic-phase disease management. However, the optimal application of RCAP for acute myocardial infarction (AMI) remains unknown in Japan, and therefore a nationwide survey of hospitals was conducted. METHODS AND RESULTS: In 2009, questionnaires were sent to 1,240 cardiology training hospitals authorized by the Japanese Circulation Society. The response rate was 62.9% (780/1,240). Of the 780 responding hospitals, 708 treated AMI, and in these hospitals the number of AMI patients and percutaneous coronary intervention (PCI) procedures performed were, respectively, 59±52 and 200±206 per year. The implementation rate of emergency PCI was high (91%), but that of outpatient cardiac rehabilitation (OPCR) was very low (18%). The implementation rate of RCAP after AMI was significantly lower (10%) than after stroke (57%). Cardiac rehabilitation (CR) was adopted as part of RCAP in only 19% (13/70) of currently operating RCAP programs. CONCLUSIONS: This first Japanese nationwide survey of RCAP after AMI showed that in contrast to the broad dissemination of acute-phase invasive treatment for AMI, there was infrequent implementation of OPCR, RCAP after AMI, and RCAP including CR. It will be necessary to broaden the use of RCAP after AMI, including OPCR. (Circ J 2016; 80: 1750-1755).

Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation.

BACKGROUND: Although patients taking non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine coagulation monitoring, high-risk patients require monitoring to assess pharmacodynamics. METHODS: We measured (1) anti-factor Xa activity (AXA), using chromogenic assay with the HemosIL Liquid Heparin kit, (2) prothrombin time (PT), and (3) activated partial thromboplastin time (aPTT) in 188 blood samples from 70 patients with non-valvular atrial fibrillation, of whom 36 received rivaroxaban once daily and 34 received apixaban twice daily. RESULTS: After the rivaroxaban therapy, AXA ranged from 0 to 3.65 IU/mL; PT, from 9.6 to 44.5 s; and APTT, from 19.3 to 69.7 s. After the apixaban therapy, AXA ranged from 0.02 to 3.18 IU/mL; PT, from 10.2 to 20.8 s; and APTT, from 21.8 to 59.8 s. At peak time, the AXA of patients who received rivaroxaban and apixaban were almost the same (2.08±0.91 IU/mL vs. 1.71±0.57 IU/mL), but the PT and APTT of patients who received rivaroxaban were more prolonged than those of patients who received apixaban (18.1±5.6 s vs. 13.8±0.9 s, p<0.001 and 40.9±7.3 s vs. 35.5±7.5 s, p<0.01, respectively). At trough time, the AXA and PT of patients who received rivaroxaban were respectively lower and shorter than those of patients who received apixaban (0.28±0.31 IU/mL vs. 1.04±0.72 IU/mL, p<0.001 and 11.9±2.0 s vs. 13.7±2.4 s, p<0.01, respectively), but the APTT of patients who received rivaroxaban and apixaban did not significantly differ (32.3±4.3 s vs. 34.3±3.8 s). CONCLUSIONS: Measurement of AXA might be useful to assess the pharmacodynamics of high-risk patients, such as high age, low body weight, and/or low renal function, and to assess the intensity of anticoagulation by using different methods of administration, such as crushed tablet via the nasogastric tube.